Upregulation of N-acetylaspartic acid resulting nitric oxide toxicity induces aspartoacylase mutations and protein interaction to cause pathophysiology seen in Canavan disease

作者：Surendran Sankar^*

来源：Medical Hypotheses, 2010, 75(6): 533-534.

DOI：10.1016/j.mehy.2010.07.017

Aspartoacylase (ASPA) converts N-acetylaspartic acid into aspartate and acetate. In Canavan disease (CD), N-acetylaspartic acid (NAA) is found to be increased and over 65 mutations including IVS4+1 G -> T, deletion of introns and exons have been reported in the ASPA gene. These changes lead to severe form or mild form of CD. The present study was aimed to understand mechanism in the cause of mutations in ASPA and pathophysiology seen in patients with CD. We have reported that elevated levels of NAA induce inducible nitric oxide (iNOS) to produce nitric oxide toxicity in CD. Nitric oxide toxicity has been shown to induce several mutations including base change G -> T and deletion and enhances protein interaction in several genes. Therefore we hypothesize that upregulation of NA

• 出版日期2010-12